TC-DTA:预测药物标结合的亲和力与变压器和卷积神经网络
IEEE transactions on nanobioscience
|August 12, 2024
概括
这项研究介绍了TC-DTA,这是一种用于预测药物向亲和力 (DTA) 的深度学习模型. TC-DTA准确预测结合强度,通过识别针对特定目标的强效药物候选人来加速药物发现.
科学领域:
- 生物信息学是一种生物信息学.
- 计算生物学 计算生物学
- 药物发现 药物发现 药物发现
背景情况:
- 药物向相互作用 (DTI) 对于药物发现至关重要.
- 传统的DTI预测通常是二进制的,但药物向亲和力 (DTA) 提供了更详细的见解.
- 准确的DTA预测可以显著加速虚拟查和药物开发.
研究的目的:
- 引入TC-DTA,这是一种用于药物标亲和力 (DTA) 预测的新型深度学习模型.
- 利用卷积神经网络 (CNN) 和变压器编码器模块进行增强的特征提取.
- 提高预测药物标结合强度的准确性和效率.
主要方法:
- 利用深度学习,结合CNN和变压器编码器模块.
- 经过加工的原料药物通过各种编码方法 SMILES 字符串和蛋白质氨基酸序列.
- 使用CNN用于药物和变压器编码器用于蛋白质的提取特征,其次是用于亲和力预测的多层感知子.
主要成果:
- 在戴维斯和KIBA数据集上,TC-DTA表现出优于基线方法 (KronRLS,SimBoost,DeepDTA) 的性能.
- 在预测结合亲和度得分方面取得了高准确性,通过MSE,CI和rm2等指标进行验证.
- 强调了CNN和变压器编码器在提取DTA有意义的序列表示中的有效性.
结论:
- TC-DTA模型显著提高了药物向亲和力预测的准确性.
- 深度学习方法,特别是使用CNN和变压器架构,为药物发现中的传统方法提供了更有效和高效的替代方案.
- TC-DTA可以加速识别高亲和度候选药物,简化药物开发管道.
相关概念视频
Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K
Protein-Drug Binding: Determination Methods
153
Determining protein-drug binding can be achieved through indirect and direct methods, each providing valuable insights into the interaction between proteins and drugs.
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
153
Drug-Receptor Interactions
5.1K
Drug-receptor interaction describes the binding of receptors by drugs, but not all drug-receptor interactions result in activation and tissue response. For instance, the binding of agonists activates the receptor to generate a cellular reaction, while antagonists bind to receptors without causing their activation.
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
5.1K
Drug-Receptor Bonds
2.8K
Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...
In...
2.8K
Ligand Binding Sites
12.8K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.8K
Targets for Drug Action: Overview
6.1K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
6.1K


